Amino acid-based biodegradable PEAs have been studied for many years due to their biocompatibility, biodegradability and mechanical properties. The presence of amide and ester bonds in PEA furnishes the PEA with a combination of properties typically exhibited by either polyesters or polyamides. Biodegradable PEA is typically synthesized with a solution polycondensation reaction of α-amino acids, aliphatic dicarboxylic acids (or dichloride of dicarboxylic acids) and diols (see Guo et al., Synthesis, Characterization, and Biodegradation of Copolymers of Unsaturated and Saturated Poly(ester amide)s. Journal of Polymer Science, Part A: Polymer Chemistry 2007; 45(9): 1595-1606).
PEA homopolymers generally do not have any functional groups located either along the PEA backbone chain or as pendant groups. However, the presence of functional pendant groups along the PEA backbone or as pendant groups could significantly expand the utility of PEA.
For example, functional groups would allow further chemical conjugations with a wide variety of drugs, biologically agents and/or active agents, thereby providing a novel route toward functionalized biomaterials. Built-in functional groups in PEAs could also provide an efficient method for tailoring the properties of PEA, such as hydrophilicity, degradation rate and mechanical strength.
The first reported synthesis of functional PEAs was based on a copolymer approach. A free functional group in the form of a carboxylic acid group was introduced in the lysine segment of the PEA copolymer. (see Jokhadze et al., Synthesis and Characterization of Functional Elastomeric Poly(ester Amide Co-polymers. Journal of Biomaterials Science—Polymer Edition 2007; 18(4):411-438)
In an alternative approach, carbon-to-carbon double bonds have been positioned along the backbone of PEA to provide a reactive site for the introduction of a functional group into PEA via unsaturated diacids or/and diols. The availability of these carbon-to-carbon double bonds in turn permits the fabrication of hydrogels by photo-gelation of PEA precursors, whereas PEA based upon saturated diacids or/and diols cannot be used to form hydrogels (see Guo et al., Synthesis, Characterization, and Biodegradation of Copolymers of Unsaturated and Saturated Poly(ester amide)s. Journal of Polymer Science, Part A: Polymer Chemistry 2007; 45(9): 1595-1606).
The present invention relates to an efficient and cost effective way to produce saturated and unsaturated PEAs with free pendant functional groups.